Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions.

Abstract p73, a protein having substantial structural and functional similarity to p53, has recently been identified and demonstrated to be a potential tumor suppressor. Its location on human chromosome 1p36.33 implicates p73 as a candidate for neuroblastoma. Like neuroblastoma, oligodendrogliomas also show a high frequency of deletions in chromosome 1p36.3. To determine whether p73 is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. We first determined the genomic organization and the intron–exon boundary sequences of the p73 gene by long PCR, vectorette PCR, and Southern hybridization. This gene spans about 65 kb with a large first intron. Primer pairs for the amplification of each of the 13 p73 encoding exons were designed in corresponding introns. The amplicons were then analyzed using the denaturing high-performance liquid chromatography system for mutations in the p73 gene. Twenty oligodendroglioma samples with 1p36.3 deletions were screened, but no mutations were detected except for several polymorphisms. It is thus clear that p73 is not a candidate gene for oligodendroglioma despite its location in the frequently deleted 1p36.3 region.